We propose to purchase a high performance, multiscale, single-photon emission computed tomographic (SPECT) scanner to be used by researchers at Harvard Medical School (HMS), the Harvard School of Public Health (HSPH), and the adjacent HMS-affiliated teaching hospitals to image animals ranging in size from transgenic mice to large primates, as well as phantoms for physics research on new imaging techniques. The system will consist of a large field-of-view triple-head SPECT instrument with enhanced capability, through the addition of multiple pinhole collimators, for high-resolution (1-2 mm FWHM) imaging of rodents. This instrument will provide HMS researchers with the ability to image three-dimensional distributions of long-half-life radionuclides, as well as the capability, unique to SPECT, for simultaneous imaging of dual isotopes. The HMS campus is an ideal environment for optimal use of this instrument. The proposed location is adjacent to a 4.7T research MR animal imager, facilitating fusion of the SPECT images and MR images, and in close proximity to the Rodent Histopathology Core Facility of the Dana-Farber/Harvard Cancer Center. Also adjoining the proposed SPECT facility are the radiobiology and radiopharmaceutical chemistry groups, comprised of researchers who can radiolabel ligands with the required single-photon emitters, as well as a SPECT physics research group who will ensure state-of-the art quantitative SPECT imaging, customized for the users, by developing application-specific reconstruction algorithms, new correction methods, and new collimation tailored to certain biomedical imaging applications. The users of our research SPECT facility will pursue basic studies of molecular biology and genetics, development of new techniques for diagnosis and treatment of cancer, research on new radiopharmaceuticals for SPECT and positron emission tomographic (PET) imaging, basic studies of pulmonary physiology, research on Parkinson's disease and neurotransmission disorders, and development and testing of new techniques of correcting for systematic effects that can adversely affect the clarity and quantitative accuracy of SPECT images. The instrument will initially be used by 11 research groups, including 15 principal investigators, all of whom have their own external grant funding, primarily from the National Institutes of Health, but also from the Department of Energy, the US. Army, the Massachusetts Department of Public Health, the American Cancer Society, and the Dana Foundation.